One-phase Split-bolus CT Urography – a Novel Approach To Reduce Radiation Dose in Diagnostics of Congenital Anomalies of Kidneys and Urinary Tract in Children

Abstract Background Low-dose CT Urography (LD-CTU) has become a standard procedure in urinary tract abnormalities in children, especially when MR Urography is not available. Standard one-phase CTU is performed in excretory phase. There is also a split-bolus technique, which combines two or even three phases during one scan and provides more clinical information without higher radiation exposure. It can be implemented for congenital anomalies of kidneys and urinary tract (CAKUT) in children, however, this application is not deeply discussed in scientific literature. Aim of this publication is to present the protocol and determine the role of LD-CTU in diagnostic imaging of CAKUT in children. Material and methods Close to 300 CTUs in children were performed as a standard of care during the last 6 years in our Department. Diagnostic accuracy in suspected CAKUT was analyzed, depending on applied protocol − standard excretory CTU, multiphase CTU and two different one-phase split-bolus CTU protocols. Results Visualization of the urinary tract was adequate in all study protocols. However, more clinically significant information was received in vascular-excretory protocol, including vascular and renal anatomy. Radiation exposure was similar or even lower than in other study protocols. Conclusions One-phase split-bolus CTU protocol is a novel approach in low-dose diagnostic imaging of CAKUT in children. Combination of vascular and excretory phases has been shown as very effective technique, especially in comprehensive anatomical assessment of the abnormality and qualification to surgical intervention.


INTRODUCTION
As considered by the ESPR and ESUR groups, the only indications for CT Urography (CTU) in children include: suspected nephrolithiasis, renal trauma, some tumors and complicated infections [1,2]. MR Urography (MRU) has become a standard in other diseases or abnormalities of urinary tract in children. However, there is a role for CTU in case MRU is not available [2,3].
CTU can be routinely performed in children with suspected congenital anomalies of kidneys and urinary tract (CAKUT) [4], especially before planned surgical intervention. Shorter time of examination and no need or much shorter time of sedation, in comparison to MRU, are an advantage [3,5]. Low-dose protocols can help to achieve ALARA (as low as reasonably achievable) principle [4].
Split-bolus technique has already been described as a method of radiation dose reduction in CTU [1,2,6,7]. Contrast medium (CM) is divided in two portions and administered with a several minutes interval. e scan is performed soon a er the second dose. is allows to obtain two phases during one scan, with sparing the radiation dose. e diagnostic value of both phases is maintained. e study can be performed in di erent protocols, even as a triple-bolus one-phase CTU [3,7,8]. ey di er by contrast volume per portion and by the intervals between portions.
CTU is considered as reliable technique in diagnosis of CAKUT [9,10]. However − to the best of our knowledge -this is the rst publication describing one-phase splitbolus low dose CTU technique in diagnosis of CAKUT in children. We present our experience with LD-CTU protocol, which was developed during the last 6 years in our Department.

OBJECTIVE
To present the protocol and determine the role of LD-CTU in diagnostic imaging of CAKUT in children.

MATERIAL AND METHODS
During the last 6 years (2011-2016) we have performed 276 CTUs in 249 children. is number includes standard indications, mentioned above (renal trauma, tumors, complicated infections and nephrolithiasis), but also suspected CAKUT.
CTUs were performed with two di erent multidetector CT scanners (64-row Philips Brilliance and 320-row Toshiba Aquilion ONE).
CTU was performed in 4 di erent protocols: − Protocol 1: one-phase excretory CTU − performed 15-20 minutes a er injection of CM in dose 1 ml/kg; − Protocol 2: one-phase split-bolus CTU, with combination of parenchymal and excretory phases [6, 7] − 2-2,5 ml/kg of CM was divided half-and-half, standard time interval between CM bolus injections was 15-20 minutes, and the scan was performed 40-60s a er second dose of CM; − Protocol 3: one-phase split-bolus CTU, with combination of vascular and excretory phases ( g. 1) − protocol was similar to no. 2, however, scan was performed 20-35s a er second dose of CM bolus injection, so earlier than in parenchymal phase. An automated bolus tracking system was also used in several studies, with ROI placed in descending aorta at the level of the diaphragm. − Protocol 4: excretory phase was performed as a part of a multiphase study. Whenever possible, low acquisition parameters were used, to meet ESPR and ESUR criteria [1, 2] and our guidelines described in previous publications [4].
CTU protocol evolved in time, and in some cases it could slightly di er from mentioned above -this concerned especially doses of CM per phase and time intervals between CM bolus injections (i.e. it could be elongated in some patients with severe hydronephrosis).
Examinations performed due to suspected CAKUT and follow-up studies performed a er surgical repair were chosen to the nal analysis − that is 226 CTUs in 205 patients (190 CTUs performed on Philips Brilliance, 36 -on Toshiba Aquilion ONE). In most cases, CTU was performed if no correlation was observed between the results of di erent imaging studies (especially ultrasonography and dynamic scintigraphy) or before quali cation for surgical repair of the abnormality. Whenever possible, CTU was performed as a one-phase study.

RESULTS
In all study protocols, visualization of the urinary tracts was adequate to make the correct diagnosis and select an appropriate management method.
Indications for the CTUs in all study protocols are listed in table I. Most CTUs were performed only in excretory phase (Protocol 1 − 104 examinations), while 88 in split-bolus technique. is number contains parenchymal-excretory protocol (Protocol 2 − 33 CTUs) and vascular-excretory protocol (Protocol 3 -55 CTUs). 34 examinations were performed as a part of a multiphase study (two or more phases, with at least one excretory phase) -Protocol 4.
In the group of 105 children with hydronephrosis, 62 were quali ed for surgical treatment, while the remaining group was quali ed for further observation. ere were 15 patients with suspected crossing vessel as the cause of hydronephrosis (four patients in Protocol 1, eight patients in Protocol 3 and three patients in Protocol 4). Only Protocol 3 directly visualized the crossing vessel, while in Protocols 1 and 4 -there were only indirect signs, like compression of the ureter's contour (none of 3 CTUs in Protocol 4 was performed with a vascular phase).
In 50 patients with suspected duplication of the urinary tract, the abnormality was ruled out in 12 children (four patients in Protocol 1, six patients in Protocol 2, one patient in Protocol 3 and one patient in Protocol 4). 24 patients were quali ed to surgical repair (heminephrectomy).
ere were complications in 4 children, due to suspected post-operative urine leakage from the cut surface -preoperative CTUs were performed in Protocol 1 (two cases), Protocol 2 (one case) and Protocol 3 (one case). Urine leakage was con rmed in post-operative CTUs in 3 children (two examinations performed in Protocol 1, one examination in Protocol 4) -surgical revision was performed in all patients. One CTU, performed in Protocol 1, ruled out the urine leakage.

DISCUSSION
e role of CTU in children is di erent than in adults, where optimal distention and opaci cation of the collecting system, ureters and urinary bladder is essential for detection of urothelial cancer [7]. In diagnosis of CAKUT in children, it is crucial to visualize the anatomy of the abnormality, therefore MRU has become a method of choice [11][12]. However, in many clinical situations LD-CTU could be performed instead of MRU.
Our analysis of the diagnostic accuracy of CTUs performed in di erent protocols showed that all of them provide adequate visualization of the urinary tract. However, there is a signi cant di erence when the complete urinary system must be assessed, including vascular and renal anatomy.
One-phase excretory CTU (Protocol 1) is a standard procedure in CAKUT diagnosis [4]. However, it provides information only about collecting systems, ureters and urinary bladder, and in some cases additional scans in di erent phases are necessary. is will multiply radiation dose. Split-bolus technique has been already described as a method of radiation dose reduction in CTU [1,2,6,7]. ere are several protocols, in CT or MR Urography, with di erent combinations of vascular, parenchymal and excretory phases [6][7][8], but -to the best of our knowledge − it was not described for diagnosis of CAKUT in children.

IndicaƟon/Wskazanie
Combination of parenchymal and excretory phases (Protocol 2) in most analyzed cases did not bring more clinical information. Enhancement of renal parenchyma may reveal renal scars or focal lesions, however, this is not a main goal in suspected CAKUT. Renal scars will be evaluated in scintigraphy or MRU, while focal lesions are not routinely suspected in such patients. However, parenchymal enhancement can help to visualize general renal anatomy before planned surgical intervention.
Combination of vascular and excretory phases (Protocol 3) provides the most complex visualization of the urinary system. It allows to asses abnormalities of the collecting system, with additional information about renal vascularity and general renal anatomy. It appears very useful especially before planned surgical intervention, e.g. heminephrectomy in duplicated collecting systems, where renal vessels and borders between both parts of the kidney should be evaluated ( g. 2). Vascular phase in this technique is not a "pure" CT-angiography, and it allows to assess renal parenchyma as well -higher heart rates in children will early enhance renal parenchyma in cortico-medullary phase [13]. Also, this protocol allows to detect crossing vessels as the cause of hydronephrosis [14][15]. In comparison to other protocols, Protocol 3 will directly visualize the additional renal artery crossing and compressing the proximal ureter ( g. 3).
Multiphase CTU (Protocol 4) exposes the patient to higher radiation doses (which are multiplied with every additional phase) and should not be routinely performed  in children. Similar diagnostic accuracy can be obtained in one-phase studies. In our material, implementation of both split-bolus techniques (Protocol 2 and Protocol 3) allowed to more accurately assess the kidney anatomy and it was a milestone in planning the surgery, as assessed by the urologists. Due to additional visualization of renal vessels, Protocol 3 (combination of vascular and excretory phases) appears as more e ective split-bolus CTU technique. It must be emphasized, however, that study protocol must suit the diagnostic problem. In case of suspected urine leakage a er surgery (e.g. heminephrectomy), we suggest to perform the follow-up post-operative CTU in a single excretory phase (Protocol 1), as parenchymal enhancement in split-bolus technique may obscure the leakage.
Our analysis showed that one-phase split-bolus LD-CTU protocol is a very e ective and dose sparing technique in diagnosis of CAKUT in children. Additionally, it can be adapted to the standard indications agreed by the ESPR and ESUR groups [1,2]. In renal trauma, not only renal parenchyma can be assessed during one scan, but also vessels and collecting system ( g. 4) [1,2,7]. is will reduce the need of multiple scanning, especially that initially the site of injury may be not known. In imaging diagnosis of tumors and complicated infections, parenchymal phase is considered su cient in most cases [1,2]. However, in some speci c situations additional scans can be required. e primary role of imaging in renal tumors in children is the pre-operative assessment and evaluation for metastatic disease [16], including venous invasion. During diagnosis of complicated pyelonephritis, the site of obstruction or congenital abnormality which predisposes to infection [5] can be revealed with onephase split bolus technique.
ere were limitations to our study. We haven't compared directly the image quality and dose reduction between the study protocols, or di erences in diagnostic accuracy between both CT scanners. e main goal was to present advantages of one-phase split-bolus CTU technique. In comparison to multiphase studies, where the radiation dose multiplies with every additional phase, implementation of one-phase CTU protocol allowed to signi cantly reduce  radiation dose. Furthermore, in comparison to di erent CTU protocols, diagnostic accuracy increased signi cantly when the one-phase split-bolus CTU with combination of vascular and excretory phases was implemented. is protocol is universal and can be adapted to every CT scanner, nevertheless, there are still many issues for further investigations, especially with protocol optimization (e.g. evaluation of image quality in lower dose examinations). Also, the optimal use of CM should be evaluated, especially in terms of CM volume and time interval between CM bolus injections. From our experience, it is recommended to use at least 2 ml/kg of total dose of CM, divided halfand-half for vascular and excretory phases. Lower doses, like standard 1 -1,5 ml/kg divided for both phases, could be not su cient to appropriately enhance renal vessels, parenchyma and collecting system, especially in case of hydronephrosis.

CONCLUSIONS
Low-dose one-phase split-bolus CTU protocol is a reliable technique to reduce radiation dose in children. Combination of vascular and excretory phases provides very precise picture of CAKUT, especially before planned surgical intervention. It can become a standard CTU protocol in children.